{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,15]],"date-time":"2026-07-15T14:44:28Z","timestamp":1784126668350,"version":"3.55.0"},"reference-count":52,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"7","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Circulation Research"],"published-print":{"date-parts":[[2020,3,27]]},"abstract":"<jats:sec>\n                    <jats:title>Rationale:<\/jats:title>\n                    <jats:p>Mesenchymal stromal cell\u2013based therapy is promising against ischemic heart failure. However, its efficacy is limited due to low cell retention and poor paracrine function. A transmembrane protein capable of enhancing cell-cell adhesion, N-cadherin garnered attention in the field of stem cell biology only recently.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objective:<\/jats:title>\n                    <jats:p>The current study investigates whether and how N-cadherin may regulate mesenchymal stromal cells retention and cardioprotective capability against ischemic heart failure.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and Results:<\/jats:title>\n                    <jats:p>Adult mice\u2013derived adipose tissue\u2013derived mesenchymal stromal cells (ADSC) were transfected with adenovirus harboring N-cadherin, T-cadherin, or control adenovirus. CM-DiI-labeled ADSC were intramyocardially injected into the infarct border zone at 3 sites immediately after myocardial infarction (MI) or myocardial ischemia\/reperfusion. ADSC retention\/survival, cardiomyocyte apoptosis\/proliferation, capillary density, cardiac fibrosis, and cardiac function were determined. Discovery-driven\/cause-effect analysis was used to determine the molecular mechanisms. Compared with ADSC transfected with adenovirus-control, N-cadherin overexpression (but not T-cadherin) markedly increased engrafted ADSC survival\/retention up to 7 days post-MI. Histological analysis revealed that ADSC transfected with adenovirus-N-cadherin significantly preserved capillary density and increased cardiomyocyte proliferation and moderately reduced cardiomyocyte apoptosis 3 days post-MI. More importantly, ADSC transfected with adenovirus-N-cadherin (but not ADSC transfected with adenovirus-T-cadherin) significantly increased left ventricular ejection fraction and reduced fibrosis in both MI and myocardial ischemia\/reperfusion mice. In vitro experiments demonstrated that N-cadherin overexpression promoted ADSC-cardiomyocyte adhesion and ADSC migration, enhancing their capability to increase angiogenesis and cardiomyocyte proliferation. MMP (matrix metallopeptidases)-10\/13 and HGF (hepatocyte growth factor) upregulation is responsible for N-cadherin\u2019s effect upon ADSC migration and paracrine angiogenesis. N-cadherin overexpression promotes cardiomyocyte proliferation by HGF release. Mechanistically, N-cadherin overexpression significantly increased N-cadherin\/\u03b2-catenin complex formation and active \u03b2-catenin levels in the nucleus. \u03b2-catenin knockdown abolished N-cadherin overexpression\u2013induced MMP-10, MMP-13, and HGF expression and blocked the cellular actions and cardioprotective effects of ADSC overexpressing N-cadherin.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions:<\/jats:title>\n                    <jats:p>We demonstrate for the first time that N-cadherin overexpression enhances mesenchymal stromal cells\u2013protective effects against ischemic heart failure via \u03b2-catenin-mediated MMP-10\/MMP-13\/HGF expression and production, promoting ADSC\/cardiomyocyte adhesion and ADSC retention.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1161\/circresaha.119.315806","type":"journal-article","created":{"date-parts":[[2020,3,18]],"date-time":"2020-03-18T14:32:15Z","timestamp":1584541935000},"page":"857-874","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":89,"title":["N-Cadherin Overexpression Mobilizes the Protective Effects of Mesenchymal Stromal Cells Against Ischemic Heart Injury Through a \u03b2-Catenin\u2013Dependent Manner"],"prefix":"10.1161","volume":"126","author":[{"given":"Wenjun","family":"Yan","sequence":"first","affiliation":[{"name":"From the Department of Cardiology, Xijing Hospital (W.Y., C. Lin, Y.G., Y.C., Y.X., F.Z., R.S., C. Li, L.T.), Fourth Military Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chen","family":"Lin","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Xijing Hospital (W.Y., C. Lin, Y.G., Y.C., Y.X., F.Z., R.S., C. Li, L.T.), Fourth Military Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yongzhen","family":"Guo","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Xijing Hospital (W.Y., C. Lin, Y.G., Y.C., Y.X., F.Z., R.S., C. Li, L.T.), Fourth Military Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Youhu","family":"Chen","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Xijing Hospital (W.Y., C. Lin, Y.G., Y.C., Y.X., F.Z., R.S., C. Li, L.T.), Fourth Military Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunhui","family":"Du","sequence":"additional","affiliation":[{"name":"Beijing Anzhen Hospital, Capital Medical University, Beijing Institute of Heart, Lung and Blood Vessel Diseases, China (Y.D.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Wayne Bond","family":"Lau","sequence":"additional","affiliation":[{"name":"Medicine and Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., Y.W., X.M.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yunlong","family":"Xia","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Xijing Hospital (W.Y., C. Lin, Y.G., Y.C., Y.X., F.Z., R.S., C. Li, L.T.), Fourth Military Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fuyang","family":"Zhang","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Xijing Hospital (W.Y., C. Lin, Y.G., Y.C., Y.X., F.Z., R.S., C. Li, L.T.), Fourth Military Medical University, China"},{"name":"Department of Physiology, School of Basic Medicine (F.Z.), Fourth Military Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renzhi","family":"Su","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Xijing Hospital (W.Y., C. Lin, Y.G., Y.C., Y.X., F.Z., R.S., C. Li, L.T.), Fourth Military Medical University, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erhe","family":"Gao","sequence":"additional","affiliation":[{"name":"Center for Translational Medicine, Lewis Katz School of Medicine at Temple University, Philadelphia, PA (E.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yajing","family":"Wang","sequence":"additional","affiliation":[{"name":"Medicine and Department of Emergency Medicine, Thomas Jefferson University, Philadelphia, PA (W.B.L., Y.W., X.M.)"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Congye","family":"Li","sequence":"additional","affiliation":[{"name":"From the Department of Cardiology, Xijing Hospital (W.Y., C. Lin, Y.G., Y.C., Y.X., F.Z., R.S., C. 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